The present invention relates to a one-pot, two-step, catalytic process to prepare 2,5-diformylfuran from a source of fructose or other carbohydrates.
2,5-(Hydroxymethyl)furfural (HMF) is a versatile intermediate that can be obtained in high yield from biomass sources such as naturally occurring carbohydrates, including fructose, glucose, sucrose, and starch. Specifically, HMF is a conversion product of hexoses with 6 carbon atoms.
2,5-Diformylfuran (DFF) has been prepared from HMF using CrO3 and K2Cr2O7 (L. Cottier et al., Org. Prep. Proced. Int. (1995), 27(5), 564; JP 54009260) but these methods are expensive and result in large amounts of inorganic salts as waste. Heterogeneous catalysis using vanadium compounds has also been used, but the catalysts have shown low turnover numbers (DE 19615878, Moreau, C. et al., Stud. Surf. Sci. Catal. (1997), 108, 399-406). Catalytic oxidation has been demonstrated using hydrogen peroxide (M. P. J. Van Deurzen, Carbohydrate Chem. (1997), 16(3), 299) and dinitrogen tetraoxide (JP 55049368) which are expensive. The relatively inexpensive molecular oxygen (O2) has been used with a Pt/C catalyst (U.S. Pat. No. 4,977,283) to form both DFF and furan-2,5-dicarboxylic acid (FDA), but yielded low amounts of DFF. 
DFF is itself a useful intermediate for many compounds. DFF has been polymerized to form polypinacols and polyvinyls, and used as a starting material for the synthesis of antifungal agents, drugs, and ligands. DFF can also be used to produce unsubstituted furan. In spite of its proven usefulness, DFF is not readily available commercially.
Selective oxidation of HMF is the only industrially feasible route to DFF. A process that converts a carbohydrate to DFF that avoids the costly HMF isolation step would have an economic advantage. French patent application 2,669,636 describes a one-pot reaction using acetic anhydride in dimethyl sulfoxide for the desired process, but includes additional process steps and is sensitive to water content. After formation of HMF, water is partially removed and an additional solvent is added.
It is therefore the object of the present invention to provide a single solvent, simple, catalytic process that can be run in the presence of water to convert a carbohydrate to DFF without the isolation of HMF.
The invention is directed to a process for the preparation of 2,5-diformylfuran comprising the steps of: a) combining a source of carbohydrate with a first solvent; b) heating the reaction mixture of step (a) at a temperature sufficient to form 2,5-hydroxymethylfurfural; c) adding an oxidant and a catalytic amount of a vanadium compound to the reaction mixture of step (b); and d) heating the reaction mixture of step (c) at a temperature sufficient to form 2,5-diformylfuran; without adding an additional solvent after steps (b), (c) or (d). Preferably the source of carbohydrate is a source of fructose. More preferably the source of fructose is selected from the group consisting of crude fructose, purified fructose, a fructose-containing biomass, corn syrup, sucrose, and polyfructanes.
Also preferred is a method wherein the solvent in step (a) is dimethylsulfoxide, and in step (b), a catalyst or promoter, preferably a cation exchange resin, is added to the first reaction mixture before heating said first reaction mixture to form the second reaction mixture. The process can also further comprise the step of removing said catalyst or promoter from the second reaction mixture before step (c).
The preferred process comprises cooling the second reaction mixture to 15xc2x0 C.-100xc2x0 C. before step (c). Preferably the temperature of step (b) is 50xc2x0 C. to 150xc2x0 C. and temperature of step (d) is 120xc2x0 C. to 180xc2x0 C. More preferably the temperature of step (d) is 140xc2x0 C. to 160xc2x0 C.
A preferred vanadium compound is selected from the group consisting of vanadium oxide or vanadium phosphorus oxide; more preferred is a vanadium compound selected from the group consisting of VO(PO3)2, (VO)2P2O7, VOPO4, VOHPO4.0.5H2O, [(VO)4(P2O7)2(OCH3)4]xe2x88x924[(C8H12N)4]+4,[(VO)12(C6H5PO3)8(OH)12]xe2x88x924[(C8H12N)4]+4, (VO)4(C12H10PO2)2(OCH3)6(CH3OH)2, and V2O5.
The process can further comprise the step of isolating and/or purifying the 2,5-diformylfuran formed in step (d).
The present invention is a process to prepare diformylfuran (DFF), also known as furan 2,5-dicarboxaldehyde, in a single pot, two step process from a source of carbohydrate. As used herein, a xe2x80x9csource of carbohydratexe2x80x9d is meant fructose, other hexoses, or any biomass that contains carbohydrates that will produce HMF upon dehydration. As used herein, by a xe2x80x9csource of fructosexe2x80x9d is meant fructose itself, purified or crude, or any biomass that contains fructose or precursors to fructose, such as corn syrup, sucrose, and polyfructanes. Preferred is high fructose corn syrup. As used herein, xe2x80x9cbiomassxe2x80x9d is meant any microbial, animal or plant-based material of carbohydrate composition including herbaceous and woody energy crops, agricultural food and feed crops, agricultural crop wastes and residues, wood wastes and residues, aquatic plants, and other waste materials including some municipal wastes.
The source of carbohydrate, preferably fructose, is mixed with a suitable solvent. The fructose itself or its precursors should be at least partially soluble in the solvent used, and preferably completely dissolved. Preferred is a single solvent, but combinations of solvents may be used. By xe2x80x9csolventxe2x80x9d is meant a single solvent or a combination of suitable solvents. Water may be present up to a concentration of about 5%. A suitable solvent is one in which the resulting HMF is fairly soluble, does not interfere with the dehydration reaction, and is stable at reaction conditions. Preferred solvents are dimethyl sulfoxide (DMSO), dimethylacetamide (DMA), sulfolane, N-methylpyrrolidinone (NMP), tetramethylurea (TMU), tributyl phosphate and dimethylformamide (DMF), and combinations thereof. Most preferred are dimethyl sulfoxide, tetramethylurea, or a combination thereof. The reaction mixture formed above is then heated to promote a dehydration reaction to produce HMF from fructose without adding any additional solvent. The water formed from the dehydration reaction is not considered an additional solvent.
A catalyst or promoter can optionally be added to the reaction mixture for the fructose to HMF reaction step. Catalysts include Bronsted and Lewis acids, transition metal salts and complexes, and ion exchange resins. These include, but are not limited to, oxalic acid, H2SO4, H3PO4, HCl, levulinic acid, p-toluene sulfonic acid, I2, ammonium sulfate, ammonium sulfite, pyridinium phosphate, pyridinium HCl, BF3 and complexes, ion-exchange resins, zeolites, and Zn, Al, Cr, Ti, Th, Zr and V salts and complexes. For other examples of catalysts and promoters, see Kuster et al., Starch 42 (1990), No. 8, pg. 314, which is hereby incorporated by reference. A preferred catalyst is a cation ion exchange resin, such as acid forms of Dowex(copyright) type ion-exchange resins (Dow Chemicals Co., Midlands, Mich.). More preferred are Bio-Rad AG-50W resins (Bio-Rad Laboratories, Hercules, Calif.).
The preferred temperature range will vary with solvent and catalyst or promoter used but is generally about 50xc2x0 C. to about 150xc2x0 C. when a catalyst or promoter is used, and is generally about 140-165xc2x0 C. when a catalyst or promoter is not used. If the reaction mixture is not already at the preferred temperature it may be heated until the desired temperature is attained. The time of reaction will vary with reaction conditions and desired yield, but is generally about 1 to about 48 hours. Agitation may also be used.
In most instances, the reaction will occur faster at higher temperatures, but higher selectivities are observed at lower temperatures. At lower temperature the reaction gives better yields but may be too slow to be practical. At higher temperatures, the reaction speeds up but also becomes less selective due to side reactions and product decomposition. Therefore, in order to obtain highest possible yields of HMF, the reaction conditions should be optimized, i.e. a temperature range should be used within which the reaction is fast enough, while producing satisfactory yields of the desired product.
The insoluble catalyst or promoter of the invention, if one is used, may be removed from the reaction mixture before proceeding to the next step. The removal can be done by any known means, such as filtering, or centrifugation and decantation. The reaction mixture can also be cooled for the removal step or before proceeding to the oxidation reaction step for ease in handling. After removal, the catalyst or promoter may be washed with additional quantities of the original solvent. The washings are then combined with the filtrate in order to minimize loss of the HMF solution produced.
The process of the invention is performed as a xe2x80x9cone-potxe2x80x9d reaction. By xe2x80x9cone-potxe2x80x9d reaction is meant that the HMF formed in the first two step of the process is not isolated from the reaction mixture. Instead, the entire reaction mixture is used in the next step of the process. The one-pot reaction eliminates the effort and expense of the HMF isolation step. However, it will be understood to persons skilled in the art that HMF may be isolated from the reaction mixture before continuing the process herein.
A heterogeneous catalyst and an oxidant are next added to the reaction mixture formed above. It is important to note that no additional solvent is added to the reaction mixture at this time. By xe2x80x9cadditional solventxe2x80x9d is meant a solvent that is different than the solvent that was originally combined with the source of carbohydrate in the first step of the process. Drying of the reaction mixture may be beneficial but is not necessary.
The catalyst comprises a vanadium oxide or vanadium phosphorus oxide compound. Other anions or ligands may be present in the vanadium compound. Suitable catalysts include, but are not limited to, VO(PO3)2, (VO)2P2O7, gamma-VOPO4, delta-VOPO4, VOHPO4.0.5H2O, [(VO)4(P2O7)2(OCH3)4]xe2x88x924[(C8H12N)4]+4, [(VO)12(C6H5PO3)8(OH)12]xe2x88x924[(C8H12N)4]+4, (VO)4(C12H10PO2)2(OCH3)6(CH3OH)2, and V2O5. Preferred is V2O5 and VOHPO4.0.5H2O.
The oxidant in the processes of the present invention is preferably an oxygen-containing gas or gas mixture, such as, but not limited to air. Oxygen by itself is also a preferred oxidant. Other oxidants that are suitable include hydrogen peroxide. The reaction mixture is then heated to oxidize the HMF to produce DFF, with no additional solvent added. Drying of the reaction mixture is not necessary.
The preferred temperature range will vary with catalyst used but is about 10xc2x0 C.-200xc2x0 C., preferably about 140xc2x0 C.-160xc2x0 C. As described above, the reaction will occur faster at higher temperatures, but higher selectivities are observed at lower temperatures. Because the HMF to DFF reaction is a heterogeneous reaction catalyzed by vanadium compounds, the time needed to reach approximately 100% conversion will depend, among other factors, on (i) reaction temperature, (ii) stirring efficiency, (iii) air/oxygen flow through the liquid phase, (iv) type of catalyst used, (v) catalyst amount, (vi) the amount of water produced in the first stepxe2x80x94large quantities of water decrease catalytic activity, (vii) catalyst dispersity, (viii) presence or absence of catalytic poisons resulting from side-products formed in the first step. The time of reaction also will vary with reaction conditions and desired yield, but is generally about 1 to about 24 hours. The reaction may be conducted under pressure of air or oxygen. Agitation may also be used.
The DFF formed above may optionally be isolated from the reaction mixture using any known means, such as but not limited to liquid-liquid extraction, vacuum distillation/sublimation of DFF, and dilution with water and extraction with a suitable organic solvent, such as dichloromethane. If dimethyl sulfoxide is used as the solvent in the reaction mixture, a preferred method is liquid-liquid extraction with a solvent such as toluene, cyclohexane, or ether.
Once isolated, the DFF may be purified by any known means, such as but not limited to vacuum sublimation, filtration in dichloromethane through silica, recrystallization, and Soxhlet extraction. When dimethyl sulfoxide is the solvent used in the reaction mixture, recrystallization using a mixture of dichloromethane and a saturated hydrocarbon such as hexane is a preferred method of purification. Soxhlet extraction is also a preferred method when using an organic solvent in the reaction mixture. The preferred organic solvent for this process is cyclohexane. In such extraction, a double thimble with the space between the outer and inner thimble being filled with silica gel is utilized. The latter method is continuous and is very convenient and efficient, producing very pure, polymer-grade DFF.